Screen detection of ductal carcinoma in situ and subsequent incidence of invasive interval breast cancers: a retrospective population-based study.

BACKGROUND: The value of screen detection and treatment of ductal carcinoma in situ (DCIS) is a matter of controversy. At present, the extent to which the diagnosis and treatment of DCIS could prevent the occurrence of invasive breast cancer in the future is not clear. We sought to estimate the association between detection of DCIS at screening and invasive interval cancers subsequent to the relevant screen. METHODS: We obtained aggregate data for screen-detected cancers from 84 local screening units within 11 regional Quality Assurance Reference Centres in England, Wales, and Northern Ireland from the National Health Service Breast Screening Programme. Data for DCIS diagnoses were obtained for women aged 50-64 years who were invited to and attended mammographic breast screening from April 1, 2003, to March 31, 2007 (4 screening years). Patient-level data for interval cancer arising in the 36 months after each of these were analysed by Poisson regression with invasive interval cancer screen detection rate as the outcome variable; DCIS detection frequencies were fitted first as a continuous and then as a categorical variable. We repeated this analysis after adjustment with both small size and high-grade invasive screen-detected cancers. FINDINGS: We analysed data for 5,243,658 women and on interval cancers occurring in the 36 months after the relevant screen. The average frequency of DCIS detected at screening was 1·60 per 1000 women screened (median 1·50 [unit range 0·54-3·56] [corrected to] per 1000 women). There was a significant negative association of screen-detected DCIS cases with the rate of invasive interval cancers (Poisson regression coefficient -0·084 [95% CI -0·13 to -0·03]; p=0·002). 90% of units had a DCIS detection frequency within the range of 1·00 to 2·22 per 1000 women; in these units, for every three screen-detected cases of DCIS, there was one fewer invasive interval cancer in the next 3 years. This association remained after adjustment for numbers of small screen-detected invasive cancers and for numbers of grade 3 invasive screen-detected cancers. INTERPRETATION: The association between screen-detected DCIS and subsequent invasive interval cancers suggests that detection and treatment of DCIS is worthwhile in prevention of future invasive disease. FUNDING: UK Department of Health Policy Research Programme and NHS Cancer Screening Programmes.

Systematic Review and Meta-Analysis of Individual Patient Data to Assess the Sensitivity of Cervical Cytology for Diagnosis of Cervical Cancer in Low- and Middle-Income Countries.

PURPOSE: To assess the sensitivity of cervical cytology to cancer by pooling individual patient cytology results from cancers diagnosed in studies that assessed cervical screening in low- and middle-income countries. METHODS: Two authors reviewed studies identified through PubMed and Embase databases. We included studies that reported cervical cytology in which at least one woman was diagnosed with cervical cancer and in which abnormal cytology results were investigated at colposcopy and through a histologic sample (if appropriate). When cytology results were not reported in the manuscript, authors were contacted. Stratified analyses and meta-regression were performed to assess sources of heterogeneity between studies. RESULTS: We included 717 cancers from 23 studies. The pooled sensitivity of cytology to cancer at a cutoff of a high-grade squamous intraepithelial lesion (HSIL) or worse was 79.4% (95% CI, 67.7% to 86.0%). Results from stratified analyses did not differ significantly, except among studies that recruited symptomatic women or women referred because of abnormal cytology, when the sensitivity of cytology was much higher (95.9%; 95% CI, 86.5% to 99.9%). The cutoff of an HSIL or worse detected 85% of the cancers that would have been detected at a cutoff of atypical squamous cells of undetermined significance or worse (relative sensitivity, 85.2%; 95% CI, 80.7% to 89.7%). CONCLUSION: Cytology at a high cutoff could be an excellent tool for targeted screening of populations at high risk of cervical cancer with a view to diagnose cancer at an earlier stage.

Estimation of overdiagnosis using short-term trends and lead time estimates uncontaminated by overdiagnosed cases: Results from the Norwegian Breast Screening Programme.

BACKGROUND: Estimating overdiagnosis in cancer screening is complicated. Using observational data, estimation of the expected incidence in the screening period and taking account of lead time are two major problems. METHODS: Using data from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening Programme, we estimated incidence trends, using age-specific trends by year in the pre-screening period (1985-95). We also estimated sojourn time and sensitivity using interval cancers only. Thus, lead time estimates were uncontaminated by overdiagnosed cases. Finally, we derived estimates of overdiagnosis separately for all cancers, and for invasive cancers only, correcting for lead time, using two different methods. RESULTS: Our results indicate that overdiagnosis of all cancers, invasive and in situ, constituted 15-17% of all screen-detected cancers in 1996-2009. For invasive cancers only, the corresponding figures were -2 to 7% in the same period, suggesting that a substantial proportion of the overdiagnosis in the Norwegian Programme was due to ductal carcinoma in situ. CONCLUSION: Using short-term trends, instead of long, prior to screening was more effective in predicting incidence in the screening epoch. In addition, sojourn time estimation using symptomatic cancers only avoids over-correction for lead time and consequently underestimation of overdiagnosis. Longer follow-up will provide more precise estimates of overdiagnosis.

Trends in aggregate cancer incidence rates in relation to screening and possible overdiagnosis: a word of caution.

BACKGROUND: Overdiagnosis in breast cancer screening is a topic of debate. Researchers often estimate trends in incidence prior to screening and project these to predict incidence during the screening epoch. METHODS: Data was obtained from the Cancer Registry of Norway and the Norwegian Breast Cancer Screening Programme. Using breast cancer incidence prior to screening in Norway (1976-1995), incidence trends were estimated from age-period and age-cohort models. These estimates were used to predict the incidence of breast cancer in five-year age and period groups in the screening epoch (1996-2009). RESULTS: Excess numbers of cancers in the screening age range (6,876 cancers), and deficits in women above and below the screening age range (1,947 cancers) were observed. However, only part of the observed differences between the observed and the expected incidence can be explained by screening, as evidenced by numbers of excess cancers greater than the numbers of screen-detected cancers in some age groups and time periods. CONCLUSION: There are potential errors in estimation of overdiagnosis from screening if individual data on screening exposure and detection mode are not taken into account. For reliable estimates of overdiagnosis, it is necessary to compare excess incidence in the screening period in those actually screened with the corresponding excess in those not screened. This is the subject of ongoing research.